The major objective of this research program is to characterize the mechanisms which determine the time course of ionic conductance change at the motor end-plate of skeletal muscle fibers during neuromuscular transmission and during the prolonged exposure to depolarizing quaternary compounds such as carbamylcholine. Of particular interest is the role and site of action of certain inorganic ions such as Ca and Na in determining the time course of carbamylcholine-induced desensitization. The studies planned for the upcoming grant period will include (a) the influence of intracellular sodium injection on carbachol-induced desensitization, (b) the influence of voltage on the time course of carbachol-induced desensitization in Na solutions and (c) the influence of voltage on the time course of end-plate currents produced by the partial agonist decamethonium. BIBLIOGRAPHIC REFERENCES: Marshall, I.G. and R.L. Parsons. The effects of tetraphenylboron on neuromuscular transmission in the frog. Br. J. Pharmac. 54:325-332, 1975. Marshall, I.G. and R.L. Parsons. The effects of tetraphenylboron on spontaneous transmitter release at the frog neuromuscular junction. Br. J. Pharmac. 54:333-338, 1975.